System and Method for Characterizing Patient Respiration

ABSTRACT

Patient respiration may be characterized using a marked respiration waveform involving a respiration waveform annotated with symbols, markers or other indicators representing one or more respiration characteristics. A respiration waveform may be acquired by sensing a physiological parameter modulated by respiration. A marked respiration waveform may be generated based on the acquired respiration waveform and one or more detected respiration waveform characteristics and/or respiration-related conditions. One or more components used to generate the marked respiratory waveform may be fully or partially implantable.

RELATED PATENT DOCUMENTS

This application is a divisional of U.S. patent application Ser. No.10/824,941, filed on Apr. 15, 2004, which claims the benefit ofProvisional Patent Application Ser. No. 60/504,228, filed on Sep. 18,2003, to which Applicant claims priority under 35 U.S.C. §120 and 35U.S.C. §119(e), respectively, and which are incorporated herein byreference in their entireties.

FIELD OF THE INVENTION

The present invention relates generally to methods and systems forcharacterizing patient respiration.

BACKGROUND OF THE INVENTION

The human body functions through a number of interdependentphysiological systems controlled through various mechanical, electrical,and chemical processes. The metabolic state of the body is constantlychanging. For example, as exercise level increases, the body consumesmore oxygen and gives off more carbon dioxide. The cardiac and pulmonarysystems maintain appropriate blood gas levels by making adjustments thatbring more oxygen into the system and dispel more carbon dioxide. Thecardiovascular system transports blood gases to and from the bodytissues. The respiration system, through the breathing mechanism,performs the function of exchanging these gases with the externalenvironment. Together, the cardiac and respiration systems form a largeranatomical and functional unit denoted the cardiopulmonary system.

Various disorders may affect the cardiovascular, respiratory, and otherphysiological systems. For example, heart failure (HF) is a clinicalsyndrome that impacts a number of physiological processes. Heart failureis an abnormality of cardiac function that causes cardiac output to fallbelow a level adequate to meet the metabolic demand of peripheraltissues. Heart failure is usually referred to as congestive heartfailure (CHF) due to the accompanying venous and pulmonary congestion.Congestive heart failure may have a variety of underlying causes,including ischemic heart disease (coronary artery disease), hypertension(high blood pressure), and diabetes, among others.

There are a number of diseases and disorders that primarily affectrespiration, but also impact other physiological systems. Emphysema andchronic bronchitis are grouped together and are known as chronicobstructive pulmonary disease (COPD). Pulmonary system disease alsoincludes tuberculosis, sarcoidosis, lung cancer, occupation-related lungdisease, bacterial and viral infections, and other conditions.

Chronic obstructive pulmonary disease generally develops over manyyears, typically from exposure to cigarette smoke, pollution, or otherirritants. Over time, the elasticity of the lung tissue is lost, and thelungs become distended, unable to expand and contract normally. As thedisease progresses, breathing becomes labored, and the patient growsprogressively weaker.

Disordered breathing is a respiratory system condition that affects asignificant percentage of patients between 30 and 60 years. Disorderedbreathing, including apnea and hypopnea, may be caused, for example, byan obstructed airway, or by derangement of the signals from the braincontrolling respiration. Sleep disordered breathing is particularlyprevalent and is associated with excessive daytime sleepiness, systemichypertension, increased risk of stroke, angina, and myocardialinfarction. Disordered breathing can be particularly serious forpatients concurrently suffering from cardiovascular deficiencies.

Various types of disordered respiration have been identified, including,apnea (interrupted breathing), hypopnea (shallow breathing), tachypnea(rapid breathing), hyperpnea (heavy breathing), and dyspnea (laboredbreathing). Combinations of the respiratory cycles described above maybe observed, including, for example, periodic breathing andCheyne-Stokes respiration (CSR). Cheyne-Stokes respiration isparticularly prevalent among heart failure patients, and may contributeto the progression of heart failure.

Because of the complex interactions between the cardiovascular,pulmonary, and other physiological systems, as well as the need forearly detection of various respiration diseases and disorders, aneffective approach to monitoring and early diagnosis is needed.Accurately characterizing patient respiration aids in monitoring anddiagnosing respiration-related diseases or disorders. Evaluating patientrespiration information may allow an appropriate therapy to be selectedand/or the effectiveness of a delivered therapy to be enhanced.

SUMMARY OF THE INVENTION

Various embodiments of the invention are directed to characterizingrespiration using a marked respiration waveform. In accordance with oneembodiment, a method for characterizing respiration includes acquiring arespiration waveform. One of more characteristics associated with thepatient's respiration are detected. A marked respiration waveform isgenerated using the respiration waveform and one or more symbolsindicating the one or more characteristics associated with the patientrespiration. At least one of acquiring the respiration waveform,detecting the one or more characteristics associated with therespiration, and generating the marked respiration waveform is performedat least in part implantably.

Another embodiment of the invention involves a system for characterizingpatient respiration. The system includes a respiration waveform sensorconfigured to acquire a respiration waveform. A respiration processor isconfigured to determine one or more characteristics associated with therespiration. A waveform generator is coupled to the respiration waveformsensor and the respiration processor. The waveform generator isconfigured to generate a marked respiration waveform comprising therespiration waveform and symbols indicating the one or morecharacteristics associated with the respiration. At least one of therespiration waveform sensor, the respiration processor, and the waveformgenerator includes an implantable component.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart of a method of characterizing patient respirationby generating a marked respiration waveform accordance with embodimentsof the invention;

FIG. 2 is a partial view of an implantable device that may include apatient respiration characterization system in accordance withembodiments of the invention;

FIG. 3 is a diagram illustrating an implantable transthoracic cardiacdevice that may be used in connection with characterizing patientrespiration in accordance with embodiments of the invention;

FIG. 4 is a block diagram of a medical system including a cardiac devicethat may be used to characterize patient respiration in accordance withembodiments of the invention;

FIG. 5 is a block diagram illustrating a medical system including apatient-internal device that cooperates with a patient-external deviceto implement patient respiration characterization in accordance withembodiments of the invention;

FIG. 6 is a is a graph of a respiration signal generated by atransthoracic impedance sensor that may be used in connection withcalculating respiratory characteristics and identifying disorderedbreathing in accordance with embodiments of the invention;

FIG. 7 is a graph illustrating respiration intervals used forcharacterizing patient respiration according to embodiments of theinvention;

FIG. 8 is a graph illustrating respiration patterns indicative of sleepapnea and severe sleep apnea in accordance with embodiments of theinvention;

FIGS. 9A and 9B illustrate signals characterizing normal respiration andabnormally shallow respiration utilized in accordance with embodimentsof the invention;

FIG. 10 is a flowchart illustrating a method of apnea and/or hypopneadetection according to embodiments of the invention;

FIG. 11 is a respiration graph illustrating a breath interval utilizedin connection with characterizing disordered respiration in accordancewith embodiments of the invention;

FIG. 12 is a respiration graph illustrating a hypopnea characterizationapproach in accordance with embodiments of the invention;

FIGS. 13 and 14 provide charts illustrating classification of individualdisordered breathing events and series of periodically recurringdisordered breathing events, respectively, in accordance withembodiments of the invention;

FIGS. 15A-E provide graphs illustrating respiration patterns ofdisordered breathing episodes that may be detected and characterized inaccordance with embodiments of the invention;

FIG. 15F is a graph illustrating a respiration pattern indicative ofperiodic breathing in accordance with embodiments of the invention;

FIG. 15G is a graph illustrating a respiration pattern indicative ofCheyne-Stokes respiration in accordance with embodiments of theinvention;

FIGS. 16A and 16B are graphs of representative accelerometer signalsassociated with chest wall motion for central and obstructive disorderedbreathing events, respectively, in accordance with embodiments of theinvention;

FIG. 17A illustrates a marked respiration waveform in accordance withembodiments of the invention; and

FIG. 17B illustrates a marked respiration waveform including respirationand ECG graphs in accordance with embodiments of the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings that form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Embodiments of the invention involve generating a marked respirationwaveform. The marked respiration waveform may characterize a patient'snormal respiration, disordered respiration episodes, or otherrespiration events. For example, a marked respiration waveformrepresenting normal respiration may include a time-based graph of thepatient's respiration cycles with symbols indicating variouscharacteristics of the respiration such as rate, tidal volume, minuteventilation, expiration slope, expiration volume, and/or otherrespiration characteristics or conditions.

If the patient's respiration is abnormal, the marked respirationwaveform may include symbols indicating the respiration parameterslisted above in addition to symbols further characterizing respirationabnormalities or conditions affecting the respiration. For example, inthe case of a disordered breathing episode, the marked respirationwaveform may include symbols characterizing the severity, frequency,duration, and/or type of disordered breathing.

Additionally, or alternatively, the marked respiration waveform mayinclude symbols that provide information about one or more conditionsaffecting the patient's respiration, e.g., pollution index, sleep state,and/or posture. A marked respiration waveform representing therespiration of a patient suffering from a pulmonary disease, forexample, may include symbols characterizing various respirationparameters or other conditions associated with the disease, e.g.,pulmonary congestion and/or body temperature.

The symbols used to mark the respiration waveform may comprise icons,graphics, alphanumeric characters, or other markers. The symbols may bepositioned relative to the respiration waveform to indicate a time ofoccurrence of the particular parameter indicated by the symbol. A symbolmay comprise a icon, graphic, numerical value and/or a textualdescriptor associated with a respiration characteristic, e.g., averagerespiration rate, expiratory slope, etc.

FIG. 1 is a flow chart of a method of generating a marked respirationwaveform in accordance with embodiments of the invention. The methodinvolves acquiring 120 a respiration waveform. A respiration waveformmay be acquired by sensing a signal modulated by patient respiration,such as airflow or transthoracic impedance, for example. The methodfurther includes detecting 130 one or more characteristics associatedwith the patient respiration. The one or more characteristics associatedwith the patient respiration may comprise parameters associated with therespiration waveform morphology and/or a variety of conditions affectingthe patient.

In various embodiments, the respiration characteristics may includeconditions associated with the respiration, for example, physiologicalconditions and/or contextual, non-physiological conditions present atthe time of the respiration. Physiological conditions may include bloodchemistry, expired CO2, patient posture, activity, and/or otherconditions. Contextual conditions may involve the ambient environment ofthe patient, such as ambient humidity, temperature, and/or pollutionindex, for example.

The respiration characteristics may include parameters of therespiration waveform morphology, including expiration and inspirationslope. The respiration characteristics may include characteristics ofthe respiration derived from the respiration waveform, e.g., respirationrate, tidal volume, minute ventilation, and breath intervals.Additionally or alternatively, the respiration characteristics mayinvolve symptoms or physiological conditions that may be derived ordetected from the respiration waveform, e.g., pulmonary congestion, ordisordered breathing episodes. The respiration characteristics may alsoinclude parameters characterizing respiration abnormalities, such as theduration, severity, frequency, and/or type of disordered breathing.

The acquired respiration waveform and the detected characteristics ofpatient respiration may be used to generate 140 a marked respirationwaveform. The marked respiration waveform includes the acquiredrespiration waveform and one or more symbols or other indicatorsrepresentative of the respiration characteristics. In oneimplementation, the symbols may be used to indicate discrete portions ofthe respiration waveform corresponding to the occurrence of therespiration characteristics. In another implementation, the symbols mayindicate general respiration conditions or characteristics that pertainglobally to a continuous portion the respiration waveform. Variousrespiration information, including the acquired respiration waveform,information associated with the respiration characteristics, and/or themarked respiration waveform may be stored in memory, transmitted to aseparate device, displayed on a computer screen or other type ofdisplay, and/or printed for example.

In one implementation, the system for generating a marked respirationwaveform may be implantable or include an implantable component. Animplantable system for generating a marked respiration waveform may beimplemented, for example, as a component of a cardiac device such as apacemaker, defibrillator, cardiac resynchronizer, implantable cardiacmonitor, or other implantable cardiac device.

In another example, the system for generating the marked respirationwaveform may be implemented using both patient-internal andpatient-external devices operating in coordination. In this example, afirst set of components of a marked respiration waveform system may beimplemented in one or more patient-internal devices and a second set ofcomponents of the marked respiration waveform system may be implementedin one or more patient-external devices. In various configurations, thepatient-internal and patient-external devices may communicate throughwired or wireless communication links to accomplish marked respirationwaveform generation.

FIG. 2 is a partial view of an implantable device that includes a systemfor generating a marked respiration waveform in accordance withembodiments of the invention. In this example, the implantable devicecomprises a cardiac rhythm management device (CRM) 200 comprising animplantable pulse generator 205 electrically and physically coupled toan intracardiac lead system 210. The marked respiration waveform systemmay alternatively be implemented in a variety of implantable monitoring,diagnostic, and/or therapeutic devices, such as an implantable cardiacmonitoring device, or an implantable drug delivery device, for example.

Portions of the intracardiac lead system 210 are inserted into thepatient's heart 290. The intracardiac lead system 210 includes one ormore electrodes configured to sense electrical cardiac activity of theheart, deliver electrical stimulation to the heart, and/or to sense thepatient's transthoracic impedance. Portions of the housing 201 of thepulse generator 205 may optionally serve as a can electrode.

Communications circuitry is disposed within the housing 201 forfacilitating communication between the pulse generator 205 and anexternal communication device, such as a portable or bed-sidecommunication station, patient-carried/worn communication station, orexternal programmer, for example. The communications circuitry can alsofacilitate unidirectional or bidirectional communication with one ormore external, cutaneous, or subcutaneous physiologic or non-physiologicsensors, patient-input devices, and/or information systems.

The pulse generator 205 may optionally incorporate a motion detector 220that may be used to sense various respiration-related conditions. Forexample, the motion detector 220 may be configured to sense thepatient's activity level and/or the patient's chest wall movementsassociated with respiratory effort. The motion detector 220 may beimplemented as an accelerometer positioned, for example, in or on thehousing 201 of the pulse generator 205.

The CRM 200 may incorporate a transthoracic impedance sensor that may beused to acquire the patient's respiration waveform. The transthoracicimpedance sensor may include, for example, one or more intracardiacimpedance electrodes 231-233 positioned in one or more chambers of theheart 290. The intracardiac impedance electrodes 231-233 may be coupledto impedance drive/sense circuitry 230 positioned within the housing ofthe pulse generator 205.

In one implementation, impedance drive/sense circuitry 230 generates acurrent that flows through the tissue between an impedance driveelectrode 233 and a can electrode on the housing 201 of the pulsegenerator 205. The voltage at an impedance sense electrode 231, 232relative to the can electrode changes as the patient's transthoracicimpedance changes. The voltage signal developed between the impedancesense electrode 231, 232 and the can electrode is detected by theimpedance sense circuitry 230.

The voltage signal developed at the impedance sense electrode, 231, 232,illustrated in FIG. 6, is proportional to the patient's transthoracicimpedance and represents the patient's respiration waveform. Thetransthoracic impedance increases during respiratory inspiration 610yielding a waveform with a positive slope 615. The transthoracicimpedance decreases during respiratory expiration 620 yielding a portionof the waveform having a negative slope 625. The peak-to-peak transition630 of the transthoracic impedance is proportional to the amount of airmoved in one breath, denoted the tidal volume. The amount of air movedper minute is denoted the minute ventilation. A normal “at rest”respiration pattern, e.g., during non-REM sleep, includes regular,rhythmic inspiration—expiration cycles without substantialinterruptions, as indicated in FIG. 6.

Returning to FIG. 2, the lead system 210 may include one or more cardiacpace/sense electrodes 251-255 positioned in, on, or about one or moreheart chambers for sensing electrical signals from the patient's heart290 and/or delivering pacing pulses to the heart 290. The intracardiacsense/pace electrodes 251-255, such as those illustrated in FIG. 2, maybe used to sense and/or pace one or more chambers of the heart,including the left ventricle, the right ventricle, the left atriumand/or the right atrium. The lead system 210 may include one or moredefibrillation electrodes 241, 242 for deliveringdefibrillation/cardioversion shocks to the heart.

The pulse generator 205 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 210. The pulse generator 205 may alsoinclude a marked respiration waveform system 235 for generating markedrespiratory waveforms in accordance with embodiments of the invention.Although methods for sensing respiration described in this exampleinvolve transthoracic impedance measurements, other processes foracquiring a respiration waveform are also possible, including, forexample, sensing respiration sounds and/or blood oxygen measurements,among other methods.

FIG. 3 is a diagram illustrating an implantable transthoracic cardiacdevice that may be used in connection with generating a markedrespiration waveform in accordance with embodiments of the invention.The implantable device illustrated in FIG. 3 is an implantabletransthoracic cardiac sensing and/or stimulation (ITCS) device that maybe implanted under the skin in the chest region of a patient. The ITCSdevice may, for example, be implanted subcutaneously such that all orselected elements of the device are positioned on the patient's front,back, side, or other body locations suitable for sensing cardiacactivity and delivering cardiac stimulation therapy. It is understoodthat elements of the ITCS device may be located at several differentbody locations, such as in the chest, abdominal, or subclavian regionwith electrode elements respectively positioned at different regionsnear, around, in, or on the heart.

Components of the cardiac sensing system, for example, may be positionedwithin the primary housing of the ITCS device. The primary housing(e.g., the active or non-active can) of the ITCS device, for example,may be configured for positioning outside of the rib cage at anintercostal or subcostal location, within the abdomen, or in the upperchest region (e.g., subclavian location, such as above the third rib).In one implementation, one or more electrodes may be located on theprimary housing and/or at other locations about, but not in directcontact with the heart, great vessel or coronary vasculature.

In another implementation, one or more electrodes may be located indirect contact with the heart, great vessel or coronary vasculature,such as via one or more leads implanted by use of conventionaltransvenous delivery approaches. In another implementation, for example,one or more subcutaneous electrode subsystems or electrode arrays may beused to sense cardiac activity and deliver cardiac stimulation energy inan ITCS device configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart.

In particular configurations, the ITCS device may perform functionstraditionally performed by cardiac rhythm management devices, such asproviding various cardiac monitoring, pacing and/orcardioversion/defibrillation functions. Exemplary pacemaker circuitry,structures and functionality, aspects of which can be incorporated in anITCS device of a type that may benefit from multi-parameter sensingconfigurations, are disclosed in commonly owned U.S. Pat. Nos.4,562,841; 5,284,136; 5,376,476; 5,036,849; 5,540,727; 5,836,987;6,044,298; and 6,055,454, which are hereby incorporated herein byreference in their respective entireties. It is understood that ITCSdevice configurations can provide for non-physiologic pacing support inaddition to, or to the exclusion of, bradycardia and/or anti-tachycardiapacing therapies. Exemplary cardiac monitoring circuitry, structures andfunctionality, aspects of which can be incorporated in an ITCS of thepresent invention, are disclosed in commonly owned U.S. Pat. Nos.5,313,953; 5,388,578; and 5,411,031, which are hereby incorporatedherein by reference in their respective entireties.

An ITCS device can incorporate circuitry, structures and functionalityof the subcutaneous implantable medical devices disclosed in commonlyowned U.S. Pat. Nos. 5,203,348; 5,230,337; 5,360,442; 5,366,496;5,397,342; 5,391,200; 5,545,202; 5,603,732; and 5,916,243 and commonlyowned U.S. patent application Ser. No. 60/462,272, filed Apr. 11, 2003,and Ser. No. 10/462,001, filed Jun. 13, 2003, now U.S. Publication No.2004/0230229 and Ser. No. 10/465,520, filed Jun. 19, 2003, now U.S.Publication No. 2004/0230230, which are incorporated by reference.

The ITCS device may incorporate circuitry for generating a markedrespiration waveform. In one configuration, components of the markedrespiration waveform system 303 may be positioned within the primaryhousing 302 of the ITCS device. A transthoracic impedance sensor usedfor acquiring a respiration waveform may be implemented using impedanceelectrodes 308, 309 and/or can electrode coupled to transthoracicimpedance circuitry, respiration processor, and waveform generatorwithin the primary housing 302 of the ITCS device.

An impedance sensor may include the impedance drive/sense circuitrycoupled to impedance electrodes 308, 309. In one configuration, theimpedance drive circuitry generates a current that flows between asubcutaneous impedance drive electrode 308 and a can electrode on theprimary housing 302 of the ITCS device. The voltage at a subcutaneousimpedance sense electrode 309 relative to the can electrode changes asthe patient's transthoracic impedance changes. The voltage signaldeveloped between the impedance sense electrode 309 and the canelectrode is sensed by the impedance drive/sense circuitry, producing arespiration waveform such as the respiration waveform depicted in FIG.6.

As previously discussed, the transthoracic impedance signal is relatedto patient respiration, with impedance increasing during respiratoryinspiration and decreasing during respiratory expiration.Characteristics associated with the respiration may be determined basedon respiration waveform morphology or based on other sensed parameters.The marked respiration waveform generator circuitry 303 produces amarked respiration waveform using respiration signals generated by thetransthoracic impedance sense circuitry and the determined respirationcharacteristics.

Communications circuitry is disposed within the housing 302 forfacilitating communication between the ITCS device and an externalcommunication device, such as a portable or bed-side communicationstation, patient-carried/worn communication station, or externalprogrammer, for example. The communications circuitry can alsofacilitate unidirectional or bidirectional communication with one ormore external, cutaneous, or subcutaneous physiologic or non-physiologicsensors.

FIG. 4 is a block diagram of a medical system 400 includingpatient-external or fully or partially implantable a medical device 400incorporating a marked respiration waveform system in accordance withembodiments of the invention. The medical device 400 may optionallyinclude a cardiac therapy circuit 415 and a cardiac sense circuit 420coupled through a lead system to cardiac electrodes 425. The cardiacelectrodes 425, illustrated in FIG. 4 may be used to electrically coupleto the patient's heart for sensing electrical cardiac signals and/ordelivering therapy to the heart in the form of electrical stimulationenergy, e.g., pacing pulses and/or defibrillation/cardioversion shocksas more fully described in connection with FIGS. 2 and 3 above.

The medical system 400 incorporates a system for generating markedrespiration waveforms. In the embodiment illustrated in FIG. 4,respiration waveforms are acquired based on signals generated by arespiration sensor 445. In a preferred embodiment, the respirationsensor comprises a transthoracic impedance sensor. Other methods ofacquiring a respiration waveform are also possible. Such methods mayinclude, for example, the use of patient-external respiratory bands,respiration flowmeter measurements, implantable or patient-externalbreath sound detection, blood oxygen levels, and/or other processes.

Various respiration-related conditions affecting the patient may beacquired using the cardiac electrodes 425, sensors 471, patient inputdevices 472 and/or other information systems 473. The sensors 471 maycomprise patient-internal and/or patient-external sensors coupledthrough leads or wirelessly to the respiration processor 431. Thepatient input device 472 allows the patient to input informationrelevant to respiration conditions. For example, the patient inputdevice 472 may be particularly useful for inputting informationconcerning patient-known information, such as information related topatient smoking, drug use, or other activities or perceptions that arenot automatically sensed or detected.

The respiration processor 431 may be coupled to other informationsystems 473, such as network-connected servers. The respirationprocessor 431 may access the information systems 473 to acquireinformation about conditions that may affect patient respiration. In oneimplementation, the respiration processor 431 accesses the informationsystems 473 to acquire information about conditions correlated to, orotherwise associated with, an increased or decreased incidence ofdisordered breathing in the patient. For example, the respirationprocessor 431 may access an air quality website to acquire the ambientpollution index. In this scenario, a particular level of pollution maybe correlated to in increased likelihood of disordered breathing.

Signals from the respiration sensor 445 and/or signals produced by oneor more additional sensors or devices 471, 425, 472, 473, may be used bythe respiration processor 431 to detect one or more characteristicsrelated to patient respiration. The respiration characteristics are usedto generate a marked respiration waveform.

In one embodiment, the respiration characteristics may includeparameters associated with the respiration waveform morphology, such aspeak inspiration, expiration slope, or inspiration slope. Therespiration characteristics may include a variety of physiologicaland/or non-physiological conditions. For example, the respirationcharacteristics may include parameters derived from the respirationwaveform, e.g., respiration rate, tidal volume, minute ventilation, orbreath intervals. Additionally or alternatively, the respirationcharacteristics may include symptoms and/or physiological conditionsderived from the respiration waveform, e.g., dyspnea, pulmonarycongestion. The respiration characteristics may includenon-physiological, contextual conditions such as pollution, ambienttemperature, and/or humidity. The respiration characteristics may alsoinclude parameters characterizing disordered breathing, such asduration, severity, frequency, and type of disordered breathing.

In another embodiment, the respiration characteristics may includeconditions associated with respiration, including, for example,physiological conditions and/or contextual, non-physiologicalconditions. Table 1 provides examples of patient conditions that may beused in connection with generation of a marked respiration waveform inaccordance with embodiments of the invention. Table 1 also providesillustrative sensing methods that may be employed to sense theconditions. The list provided in Table 1 is not exhaustive andadditional or different conditions may be used.

Respiration-related conditions that may be used to generate a markedrespiration waveform may include, for example, both physiological andnon-physiological (contextual) conditions affecting the patient.Physiological conditions may include a broad category of conditionsassociated with the internal functioning of the patient's physiologicalsystems, including the cardiovascular, respiratory, nervous, muscle andother systems. Examples of physiological conditions include bloodchemistry, patient posture, patient activity, respiration patterns,blood pressure, among others.

Contextual conditions are non-physiological conditions representingpatient-external or background conditions. Contextual conditions may bebroadly defined to include, for example, present environmentalconditions, such as patient location, ambient temperature, humidity, airpollution index. Contextual conditions may also includehistorical/background conditions relating to the patient, including thepatient's normal sleep time and the patient's medical history, forexample. Methods and systems for detecting some contextual conditions,including, for example, proximity to bed detection, are described incommonly owned U.S. patent application Ser. No. 10/269,611, filed Oct.11, 2002, now U.S. Pat. No. 7,400,928, which is incorporated byreference herein in its entirety.

TABLE 1 Sensor type or Detection Condition Type Condition methodPhysiological Cardiovascular Heart rate EGM, ECG System Heart ratevariability QT interval Ventricular filling pressure Intracardiacpressure sensor Blood pressure Blood pressure sensor Respiratory SystemSnoring Accelerometer Microphone Respiration pattern Transthoracicimpedance (Tidal volume Minute sensor (AC) ventilation Respiratory rate)Patency of upper airway Intrathoracic impedance sensor Pulmonarycongestion Transthoracic impedance sensor (DC) Nervous SystemSympathetic nerve activity Muscle sympathetic nerve Activity sensorBrain activity EEG Blood Chemistry CO2 saturation Blood analysis O2saturation Blood alcohol content Adrenalin Brain Natriuretic Peptide(BNP) C-Reactive Protein Drug/Medication/Tobacco use Muscle SystemMuscle atonia EMG Eye movement EOG Patient activity Accelerometer, MV,etc. Limb movements Accelerometer, EMG Jaw movements Accelerometer, EMGPosture Multi-axis accelerometer Contextual Environmental Ambienttemperature Thermometer Humidity Hygrometer Pollution Air qualitywebsite Time Clock Barometric pressure Barometer Ambient noiseMicrophone Ambient light Photodetector Altitude Altimeter Location GPS,proximity sensor Proximity to bed Proximity to bed sensorHistorical/Background Historical sleep time Patient input, previouslydetected sleep onset times Medical history Patient input Age Recentexercise Weight Gender Body mass index Neck size Emotional statePsychological history Daytime sleepiness Patient perception of sleepquality Drug, alcohol, nicotine use

The respiration processor 431 may optionally include a disorderedbreathing processor 436 for detecting disordered breathing episodes,including, for example, episodes of central and/or obstructivedisordered breathing including apnea, hypopnea, Cheyne-Stokesrespiration, or other types of disordered breathing. The disorderedbreathing processor 436 may also determine various characteristics ofthe disordered breathing episodes, such as the severity, frequency,duration, and other characteristics of the disordered breathing. Theoccurrences of disordered breathing and/or disordered breathingcharacteristics may be indicated in the marked respiration waveform.

The respiration waveform generator 430 uses the acquired respirationwaveform, the respiration characteristics derived from the respirationwaveform, and/or the other conditions associated with respiration togenerate a marked respiration waveform. The marked respiration waveformcomprises the respiration waveform and one or more symbols or otherindicators associated with the presence of various respiration waveformcharacteristics and/or respiration-related conditions. As illustrated inFIG. 17A, the symbols may be displayed at positions relative to themarked respiration waveform to indicate the timing of the respirationcharacteristics and/or conditions.

The medical system 400 may acquire one or more additional waveformsrepresentative of physiological and/or non-physiological conditionsaffecting the patient. The marked respiration waveform may be displayedalong with the one or more additional waveforms. The additionalwaveforms may be time aligned with the respiration waveform tofacilitate comparison, such as the ECG and respiration waveformsdepicted in FIG. 17B.

The medical system 400 may include a memory circuit 460 used to storeinformation related to respiration waveforms, including for example,information related to detected respiration characteristics,respiration-related conditions and/or marked or unmarked respirationwaveform data. Stored information may be transmitted by communicationcircuitry 450 to a remote device 455, such as a remote deviceprogrammer, a patient management server, or other computing devicethrough a wireless or wired communications link.

Various embodiments described herein may be used within the context ofan advanced patient management system. Advanced patient managementsystems involve a system of medical devices that are accessible throughvarious communications technologies. For example, patient data may bedownloaded from one or more of the medical devices periodically or oncommand, and stored at a patient information server. The physicianand/or the patient may communicate with the medical devices and thepatient information server, for example, to submit or acquire patientdata or to initiate, terminate or modify therapy.

Methods, structures, or techniques described herein relating to advancedpatient management, such as remote patient monitoring, diagnosis, and/ortherapy, or other advanced patient management methodologies canincorporate features of one or more of the following references: U.S.Pat. Nos. 6,221,011, 6,270,457, 6,280,380, 6,312,378, 6,336,903,6,358,203, 6,368,284, 6,398,728, and 6,440,066 which are incorporated byreference.

FIG. 5 is a block diagram illustrating a medical system 500 including apatient-internal device 510 that cooperates with a patient-externaldevice 520 to implement marked respiration waveform generation inaccordance with embodiments of the invention. In this example, themarked respiration waveform is displayed on a display device 560.

In one embodiment, the patient-internal device 510 may comprise, forexample, an implantable cardiac rhythm management system (CRM) such as apacemaker, defibrillator, cardiac resynchronizer, or the like. Thepatient-external device 520 may comprise, for example, an externalbreathing therapy device such as a continuous positive airway pressuredevice (CPAP), bi-level positive airway pressure device (bi-PAP) orother positive airway pressure device, generically referred to herein asxPAP devices.

An xPAP device 520 develops a positive air pressure that is delivered tothe patient's airway through tubing 552 and mask 554 connected to thexPAP device 520. Positive airway pressure devices are often used totreat disordered breathing. In one configuration, for example, thepositive airway pressure provided by the xPAP device 520 acts as apneumatic splint keeping the patient's airway open, thus reducing theseverity and/or number of occurrences of disordered breathing due toairway obstruction. In addition to delivering breathing therapy, thexPAP device 520 may provide a number of monitoring and/or diagnosticfunctions in relation to the respiratory system. For example, the xPAPdevice 520 may sense respiration, using an oxygen sensor, a microphone,a flow meter, and/or other respiration sensing methods.

Components used in connection with generating a marked respirationwaveform may be implemented within or on the patient-internal CRM 510device, within on the patient-external xPAP 520 device, or within or onboth devices. The CRM 510 and the xPAP 520 may be coupled to a remotecomputing device 530 such as a patient management server using awireless or wired link. The CRM 510 may provide a first set ofmonitoring, diagnostic, and/or therapeutic functions to the patient. ThexPAP device 520 may provide a second set of monitoring, diagnostic,and/or therapeutic functions to the patient. The CRM device 510, thexPAP device 520, or both may include sensors for sensing conditionsrelated to patient respiration such as those identified in Table 1.

In one embodiment, the CRM device 510 may sense patient respiration. Thesensed information may be transmitted to a respiration processor and/ora respiration waveform generator incorporated in the xPAP device 520 togenerate the marked respiration waveform.

In another embodiment, the xPAP device 520 may sense patientrespiration. Patient respiration information may be transmitted from thexPAP 520 device to the CRM device 510. The respiration information maybe used by a respiration processor and/or a marked respiration waveformgenerator implemented within the housing of the CRM device 510 togenerate the marked respiration waveform.

In yet another embodiment, CRM device 510 may sense a first set ofpatient conditions related to respiration and the xPAP device 520 maysense a second set of conditions related to respiration. Patientrespiration information may be transmitted from the xPAP 520 device andthe CRM device 510 to a remote device 530 that houses a respirationprocessor and/or a marked respiration waveform generator. The conditionsrelated to respiration may be used by the patient management server 530for generating a marked respiration waveform.

Data related to marked or unmarked respiration waveforms and/orrespiration characteristics may be transmitted to a separate device,stored in memory, printed, and/or displayed on a display device 560. Thedisplay device may display the marked respiration waveform including therespiration waveform annotated with symbols indicating respirationcharacteristics. A displayed symbol may comprise an icon, graphic,alphanumeric character, or other marker positioned relative to therespiration waveform to indicate a time of occurrence of the particularcharacteristic and/or condition. The displayed symbol may indicate, forexample, a numerical value or a textual description associated with therespiration characteristic, e.g., average respiration rate, expiratoryslope, etc.

In one embodiment, the marked respiration waveform may comprise symbolspositioned relative to the respiration waveform indicating one or moreepisodes of disordered breathing. Various characteristics of thedisordered breathing episodes, including numerically quantifiablecharacteristics, such as episode duration and blood oxygen saturation,and/or other detected characteristics such as disordered breathing typemay also be displayed on the display.

Disordered breathing may be identified and evaluated using variousphysiological and/or non-physiological (contextual) conditions. Table 2provides examples of how a representative subset of the conditionslisted in Table 1 may be used in connection with disordered breathingdetection and/or evaluation. It will be appreciated that patientconditions and detection methods other than those listed in Tables 1 and2 may be used and are considered to be within the scope of theinvention.

TABLE 2 Condition Examples of how condition may be used in TypeCondition disordered breathing detection Physiological Heart rateDecrease in heart rate may indicate disordered breathing episode.Increase in heart rate may indicate autonomic arousal from a disorderedbreathing episode. Decrease in heart rate may indicate the patient isasleep. Heart rate Disordered breathing causes heart rate variabilityvariability to decrease. Changes in HRV associated with sleep disorderedbreathing may be observed while the patient is awake or asleepVentricular filling May be used to identify/predict pulmonary pressurecongestion associated with respiratory disturbance. Blood pressureSwings in on-line blood pressure measures are associated with apnea.Disordered breathing generally increases blood pressure variability -these changes may be observed while the patient is awake or asleep.Snoring Snoring is associated with a higher incidence of obstructivesleep apnea and may be used to detect disordered breathing. RespirationRespiration patterns including, e.g., respiration pattern/rate rate, maybe used to detect disordered breathing episodes. Respiration patternsmay be used to determine the type of disordered breathing. Respirationpatterns may be used to detect that the patient is asleep. Patency ofupper Patency of upper airway is related to airway obstructive sleepapnea and may be used to detect episodes of obstructive sleep apnea.Pulmonary Pulmonary congestion is associated with congestion respiratorydisturbances. Sympathetic End of apnea associated with a spike in SNA.nerve activity Changes in SNA observed while the patient is awake orasleep may be associated with sleep disordered breathing CO2 Low CO2levels initiate central apnea. O2 O2 desaturation occurs during severeapnea/hypopnea episodes. Physiological Blood alcohol Alcohol tends toincrease incidence of snoring content & obstructive apnea. Adrenalin Endof apnea associated with a spike in blood adrenaline. BNP A marker ofheart failure status, which is associated with Cheyne-Stokes RespirationC-Reactive A measure of inflammation that may be related Protein toapnea. Drug/Medication/ These substances may affect the incidence ofTobacco use both central & obstructive apnea. Muscle atonia Muscleatonia may be used to detect REM and non-REM sleep. Eye movement Eyemovement may be used to detect REM and non-REM sleep. ContextualTemperature Ambient temperature may be a condition predisposing thepatient to episodes of disordered breathing and may be useful indisordered breathing detection. Humidity Humidity may be a conditionpredisposing the patient to episodes of disordered breathing and may beuseful in disordered breathing detection. Pollution Pollution may be acondition predisposing the patient to episodes of disordered breathingand may be useful in disordered breathing detection. Posture Posture maybe used to confirm or determine the patient is asleep. Activity Patientactivity may be used in relation to sleep detection. Location Patientlocation may used to determine if the patient is in bed as a part ofsleep detection. Altitude Lower oxygen concentrations at higheraltitudes tends to cause more central apnea

Detection of disordered breathing may involve comparing one condition ormultiple conditions to one or more thresholds or other indicesindicative of disordered breathing. A threshold or other indexindicative of disordered breathing may comprise a predetermined level ofa particular condition, e.g., blood oxygen level less than apredetermined amount. A threshold or other index indicative ofdisordered breathing may involve a change in a level of a particularcondition, e.g., heart rate decreasing from a sleep rate to a lower ratewithin a predetermined time interval.

In one approach, the relationships between the conditions may beindicative of disordered breathing. In this embodiment, disorderedbreathing detection may be based on the existence and relative valuesassociated with two or more conditions. For example, if condition A ispresent at a level of x, then condition B must also be present at alevel of f(x) before a disordered breathing detection is made.

The thresholds and/or relationships indicative of disordered breathingmay be highly patient specific. The thresholds and/or relationshipsindicative of disordered breathing may be determined on a case-by-casebasis by monitoring conditions affecting the patient and monitoringdisordered breathing episodes. The analysis may involve determininglevels of the monitored conditions and/or relationships between themonitored conditions associated, e.g., statistically correlated, withdisordered breathing episodes. The thresholds and/or relationships usedin disordered breathing detection may be updated periodically to trackchanges in the patient's response to disordered breathing.

In various implementations, episodes of disordered breathing may bedetected through analysis of the patient's respiration patterns. Methodsand systems of disordered breathing detection based on respirationpatterns are further described in commonly owned U.S. patent applicationSer. No. 10/309,770 filed Dec. 4, 2002, now U.S. Pat. No. 7,252,640,which is incorporated herein by reference.

In various embodiments, episodes of disordered breathing may be detectedby monitoring the respiration waveform signal generated by atransthoracic impedance sensor. In one example, when the tidal volume(TV) of the patient's respiration, as indicated by the transthoracicimpedance signal, falls below a hypopnea threshold, then a hypopneaevent is declared. A hypopnea event may be declared, for example, if thepatient's tidal volume falls below about 50% of a recent average tidalvolume or other baseline tidal volume value. If the patient's tidalvolume falls further to an apnea threshold, e.g., about 10% of therecent average tidal volume or other baseline value, an apnea event isdeclared.

In one embodiment, detection of disordered breathing involves definingand analyzing respiratory cycle intervals. FIG. 7 is a graphillustrating respiration intervals that may be used for detectingdisordered breathing according to embodiments of the invention.Respiratory intervals in a respiration cycle can be divided into aninspiration period 730 corresponding to the patient inhaling, anexpiration period 750, corresponding to the patient exhaling, and anon-breathing period 760 occurring between inhaling and exhaling.Respiration intervals are established using inspiration 710 andexpiration 720 thresholds. The inspiration threshold 710 marks thebeginning of an inspiration period 730 and is determined by thetransthoracic impedance signal rising above the inspiration threshold710. The inspiration period 730 ends when the transthoracic impedancesignal is maximum 740. A maximum transthoracic impedance signal 740corresponds to both the end of the inspiration period 730 and thebeginning of the expiration period 750. The expiration period 750continues until the transthoracic impedance falls below an expirationthreshold 720. A non-breathing period 760 starts from the end of theexpiration period 750 and continues until the beginning of the nextinspiration period 770.

Respiration patterns used for the detection of disordered breathing inthe form of sleep apnea and severe sleep apnea are illustrated in FIG.8. Patient respiration signals are monitored and the respiration cyclesare defined according to inspiration 830, expiration 850, andnon-breathing 860 periods as described in connection with FIG. 7. Acondition of sleep apnea is detected when a non-breathing period 860exceeds a first predetermined interval 890, denoted the sleep apneainterval. A condition of severe sleep apnea is detected when thenon-breathing period 860 exceeds a second predetermined interval 895,denoted the severe sleep apnea interval. For example, sleep apnea may bedetected when the non-breathing interval exceeds about 10 seconds, andsevere sleep apnea may be detected when the non-breathing intervalexceeds about 20 seconds.

Hypopnea is a condition of disordered breathing characterized byabnormally shallow breathing. FIGS. 9A-9B are graphs of tidal volumederived from transthoracic impedance measurements. The graphs comparethe tidal volume of a normal breathing cycle to the tidal volume of ahypopnea episode. FIG. 9A illustrates normal respiration tidal volumeand rate. As shown in FIG. 9B, hypopnea involves a period of abnormallyshallow respiration.

According to an embodiment of the invention, hypopnea is detected bycomparing a patient's respiratory tidal volume to a hypopnea tidalvolume threshold. The tidal volume for each respiration cycle may bederived from transthoracic impedance measurements. The hypopnea tidalvolume threshold may be established using clinical results providing arepresentative tidal volume and duration of hypopnea events. In oneconfiguration, hypopnea is detected when an average of the patient'srespiratory tidal volume taken over a selected time interval falls belowthe hypopnea tidal volume threshold.

FIG. 10 is a flow chart illustrating a method of apnea and/or hypopneadetection according to embodiments of the invention. Various thresholdsor other indices associated with patient respiration are established1001 before analyzing the patient's respiration for disordered breathingepisodes. For example, inspiration and expiration thresholds, sleepapnea interval, severe sleep apnea interval, and/or a hypopnea tidalvolume threshold may be established.

The patient's transthoracic impedance is sensed 1005 as described inmore detail above. If the transthoracic impedance reaches or exceeds1010 the inspiration threshold, the beginning of an inspiration intervalis detected 1015. If the transthoracic impedance remains below 1010 theinspiration threshold, then the impedance signal is checked 1005periodically until inspiration 1015 occurs.

During the inspiration interval, the patient's transthoracic impedanceis monitored until a maximum value of the transthoracic impedance isdetected 1020. Detection of the maximum value signals an end of theinspiration period and a beginning of an expiration period 1035.

The expiration interval is characterized by decreasing transthoracicimpedance. When the transthoracic impedance falls 1040 below theexpiration threshold, a non-breathing interval is detected 1055.

If the transthoracic impedance does not exceed 1060 the inspirationthreshold within a first predetermined interval 1065, denoted the sleepapnea interval, then a condition of sleep apnea is detected 1070. Severesleep apnea is detected 1080 if the non-breathing period extends beyonda second predetermined interval 1075, denoted the severe sleep apneainterval.

When the transthoracic impedance exceeds 1060 the inspiration threshold,the tidal volume from the peak-to-peak transthoracic impedance iscalculated, along with a moving average of past tidal volumes 1085. Thepeak-to-peak transthoracic impedance provides a value proportional tothe tidal volume of the respiration cycle. This value is compared to ahypopnea tidal volume threshold 1090. If the peak-to-peak transthoracicimpedance is consistent with the hypopnea tidal volume threshold 1090for a predetermined time 1092, then a hypopnea cycle is detected 1095.

Additional sensors, such as motion sensors and/or posture sensors, maybe used to confirm or verify the detection of a sleep apnea or hypopneaepisode. The additional sensors may be employed to prevent false ormissed detections of sleep apnea/hypopnea due to posture and/or motionrelated artifacts.

Another embodiment of the invention involves classifying respirationpatterns as disordered breathing episodes based on the breath intervalsand/or tidal volumes of one or more respiration cycles within therespiration patterns. According to this embodiment, the duration andtidal volumes associated with a respiration pattern are compared toduration and tidal volume thresholds. The respiration pattern isdetected as a disordered breathing episode based on the comparison.

According to principles of the invention, a breath interval isestablished for each respiration cycle. FIG. 11 is a respiration graphillustrating a breath interval utilized in connection withcharacterizing disordered breathing in accordance with embodiments ofthe invention. A breath interval represents the interval of time betweensuccessive breaths. A breath interval 1130 may be defined in a varietyof ways, for example, as the interval of time between successive maxima1110, 1120 of the impedance signal waveform.

Detection of disordered breathing, in accordance with embodiments of theinvention, involves the establishment of a duration threshold and atidal volume threshold. If a breath interval exceeds the durationthreshold, an apnea event is detected. Detection of sleep apnea, inaccordance with this embodiment, is illustrated in the graph of FIG. 11.Apnea represents a period of non-breathing. A breath interval 1130exceeding a duration threshold 1140 comprises an apnea episode.

Hypopnea may be detected using the duration threshold and tidal volumethreshold. A hypopnea event represents a period of shallow breathing.Each respiration cycle in a hypopnea event is characterized by a tidalvolume less than the tidal volume threshold. Further, the hypopnea eventinvolves a period of shallow breathing greater than the durationthreshold.

A respiration graph illustrating a hypopnea characterization approach inaccordance with embodiments of the invention is illustrated in FIG. 12.Shallow breathing is detected when the tidal volume of one or morebreaths is below a tidal volume threshold 1210. If the shallow breathingcontinues for an interval greater than a duration threshold 1220, thenthe breathing pattern represented by the sequence of shallow respirationcycles, is classified as a hypopnea event.

FIGS. 13 and 14 provide charts illustrating classification of individualdisordered breathing events and series of periodically recurringdisordered breathing events, respectively. As illustrated in FIG. 13,individual disordered breathing events may be grouped into apnea,hypopnea, tachypnea and other disordered breathing events. Apnea eventsare characterized by an absence of breathing. Intervals of reducedrespiration are classified as hypopnea events. Tachypnea events includeintervals of rapid respiration characterized by an elevated respirationrate.

As illustrated in FIG. 13, apnea and hypopnea events may be furthersubdivided as either central events, related to central nervous systemdysfunction, or obstructive events, caused by upper airway obstruction.A tachypnea event may be further classified as a hyperpnea event,represented by hyperventilation, i.e., rapid deep breathing. A tachypneaevent may alternatively be classified as rapid breathing, typically ofprolonged duration.

FIG. 14 illustrates classification of combinations of periodicallyrecurring disordered breathing events. Periodic breathing may beclassified as being obstructive, central or mixed in origin. Obstructiveperiodic breathing is characterized by cyclic respiratory patterns withan obstructive apnea or hypopnea event in each cycle. Central periodicbreathing involves cyclic respiratory patterns including a central apneaor hypopnea event in each cycle.

Periodic breathing may also be of mixed origin. Mixed origin periodicbreathing is characterized by cyclic respiratory patterns having amixture of obstructive and central apnea events in each cycle asillustrated in FIG. 15F. Cheyne-Stokes is a particular type of periodicbreathing involving a gradual waxing and waning of tidal volume andhaving a central apnea and hyperpnea event in each cycle as illustratedin FIG. 15G. Other manifestations of periodic breathing are alsopossible. Disordered breathing episodes may be classified based on thecharacteristic respiration patterns associated with particular types ofdisordered breathing.

As illustrated in FIGS. 15A-E, a respiration pattern detected as adisordered breathing episode may include only an apnea respiration cycle1510 (FIG. 15A), only hypopnea respiration cycles 1550 (FIG. 15D), or amixture of hypopnea and apnea respiration cycles 1520 (FIG. 15B), 1530(FIG. 15C), 1560 (FIG. 15E). A disordered breathing event 1520 may beginwith an apnea respiration cycle and end with one or more hypopneacycles. In another pattern, the disordered breathing event 1530 maybegin with hypopnea cycles and end with an apnea cycle. In yet anotherpattern, a disordered breathing event 1560 may begin and end withhypopnea cycles with an apnea cycle in between the hypopnea cycles.

Disordered breathing events may be classified as either centraldisordered breathing, obstructive disordered breathing, or a combinationof central and obstructive types. In accordance with embodiments of theinvention, symbols indicating the detection of central or obstructivedisordered breathing events may be included in a marked respirationwaveform.

Central disordered breathing events are characterized by insufficientrespiration and a concurrent lack of respiratory effort. Because thecentral nervous system signals that control breathing are interrupted,the patient's natural breathing reflex is not triggered. The patientmakes no effort to breath or the respiratory effort is otherwisedisrupted. Respiration ceases or is insufficient during the disorderedbreathing event.

An obstructive disordered breathing event may occur due to anobstruction of a patient's airway. For example, the patient's tongue orother soft tissue of the throat may collapse into the patient's airway.The breathing reflex is triggered, but respiration is disrupted becauseof the occluded airway. Disordered breathing events may include centraldisordered breathing events, obstructive disordered breathing events, ormixed disordered breathing events that are a combination of obstructiveand central types.

Classifying disordered breathing events as central, obstructive, or acombination of central and obstructive allows physicians to moreaccurately diagnose and treat disordered breathing. One method forclassifying a disordered breathing event as central or obstructiveinvolves detecting disordered breathing and detecting motion associatedwith respiratory effort. Respiratory effort may be detected, forexample, based on chest wall motion and/or abdominal motion associatedwith respiratory effort. Disordered breathing may be detected based onthe patient's respiration patterns, or by other methods describedherein. The disordered breathing event may be further classified as acentral, obstructive or mixed type based on the patient's respiratoryefforts during disordered breathing event.

In accordance with various embodiments of the invention a disorderedbreathing event may be classified as central disordered breathing orobstructive disordered breathing based on chest wall motions associatedwith respiratory effort. FIGS. 16A and 16B are graphs of representativeaccelerometer signals associated with chest wall motion for central andobstructive disordered breathing, respectively. As illustrated in FIG.16A, apnea is detected when the transthoracic impedance signal 1610remains below an inspiration threshold 1615 for a period of time greaterthan an apnea interval 1617, e.g., about 10 seconds. In this example,the apnea event is a central apnea event and the signal 1620 from anaccelerometer sensing the patient's chest wall motion also falls below amotion threshold 1625 during the period of non-respiration. The lack ofchest wall motion indicates that the patient's breathing reflex is notbeing triggered by the central nervous system, indicative of centraldisordered breathing.

FIG. 16B illustrates the accelerometer signal and transthoracicimpedance signal during obstructive apnea. Apnea is detected when thetransthoracic impedance signal 1650 remains below an inspirationthreshold 1655 for a period of time greater than an apnea interval 1657.In this example, the apnea is obstructive apnea and the signal 1660 froman accelerometer sensing the patient's chest wall motion rises above achest well motion threshold 1665 during the period of non-respiration.The chest wall motion indicates that the patient's breathing reflex isbeing triggered by the central nervous system, indicative of obstructivedisordered breathing. One or more symbols indicating the detection ofcentral or obstructive disordered breathing may be included in a markedrespiration waveform.

FIG. 17A illustrates a marked respiration waveform in accordance withembodiments of the invention. In one embodiment, information related toa marked respiration waveform may be acquired continuously as a movingsnapshot of respiration-related conditions. In another embodiment, theinformation related to the marked respiration waveform may be acquiredin response to one or more triggering events. In one example, thetriggering event may comprise an instruction from a physician or anautomatically generated instruction provided by an advanced patientmanagement system to begin data collection. In another example, thetriggering event may comprise detection of various respirationconditions, such as detection of the disordered breathing, the detectionof sleep, or the detection of a particular pulmonary condition. In thisscenario, the triggering event may initiate the collection ofrespiration-related data during an interval of time that may includetime periods prior to, during, and/or following the disordered breathingevent.

As illustrated in FIG. 17A, the marked respiration waveform 1710 maycomprise respiratory symbols positioned at locations relative to therespiration waveform to indicate the time of occurrence of respirationevents, and the time of occurrence of various respiration conditionsand/or characteristics. In the example depicted in FIG. 17A, therespiration waveform 1710 is marked with minute ventilation symbols 1720denoting peaks on the waveform and apnea markers 1730, 1735 denotingwhen an apnea event is detected 1730 and when the apnea event ends 1735.In addition, other symbols indicating respiration characteristics and/ordisordered breathing characteristics described above may be used toannotate the respiration waveform. The marked respiration waveforminformation may be stored, transmitted, printed and/or displayed on adisplay device to allow the patient's physician to view respiratorydisturbances and/or other characteristics. Generation of a markedrespiration waveform allows a clinician to view respiration disturbancesand to determine that respiration events were properly detected.Further, the marked respiration waveform may be used to guide diagnosisand therapy.

FIG. 17B provides an illustration of a marked respiration waveform inaccordance with embodiments of the invention including respiration andelectrocardiogram (ECG) graphs. The respiration waveform and ECG graph,such as the one depicted in FIG. 17B, may be produced, for example, by amedical device having a transthoracic impedance sensor and intracardiacEGM electrodes.

As illustrated in FIG. 17B, the marked respiration waveform may presentone or more additional waveforms. The additional waveforms may include,for example, waveforms depicting patient activity, posture, blood gas,blood pressure, and/or other waveforms. In FIG. 17B, an ECG is shownabove respiratory waveform 1710. The ECG is time-aligned withrespiration waveform 1710 and can be marked with indicatorscorresponding to the occurrence of breathing events, cardiac events,and/or other events. Displaying marked respiration waveforms and otherwaveforms related to patient conditions allows the patient's physicianto verify, for example, that a disordered breathing event was properlydetected. This confirmation may be used to enhance diagnosis and/ortherapy. Symbols indicating characteristics and/or conditions related tothe cardiovascular, respiratory and/or other physiological systemsprovide further diagnostic information for physicians. For example,annotated waveforms allow a physician to evaluate the impact ofrespiration events on other physiological systems.

As previously mentioned, changes in various respiration-relatedconditions occur or are more likely to occur during sleep. For example,episodes of disordered breathing can occur when the patient is awake,however, disordered breathing most frequently occurs during sleep. Theonset and termination or sleep, sleep stages and/or sleep qualitycharacteristics may be indicated or otherwise used in the generation ofmarked respiratory waveform. Methods and systems for detecting sleep,aspects of which may be utilized in the generation of a markedrespiration waveform, are described in commonly owned U.S. patentapplication Ser. No. 10/309,771, filed Dec. 4, 2002, now U.S. Pat. No.7,189,204, which is incorporated by reference. Methods and systems fordetecting REM sleep and/or other sleep states are described in commonlyowned U.S. patent application Ser. No. 10/643,006, filed Aug. 18, 2003,now U.S. Publication No. 2005/0043652, which is incorporated byreference. Methods and systems for evaluation of sleep qualitycharacteristics which may be used to generate a marked respiratorywaveform are described in commonly owned patent application Ser. No.10/642,998, filed Aug. 18, 2003, now U.S. Publication No. 2005/0042589,which is incorporated by reference.

Prediction of disordered breathing may trigger the generation of amarked respiration waveform. Further, symbols indicating a prediction ofdisordered breathing and/or other physiological events may be used toannotate the marked respiration waveform of the present invention.Disordered breathing prediction methods and systems, aspects of whichmay be utilized in connection with generating a marked respirationwaveform, are described in commonly owned U.S. patent application Ser.No. 10/643,016, filed Aug. 18, 2003, now U.S. Pat. No. 7,396,333, whichis incorporated herein by reference.

A number of the examples presented herein involve block diagramsillustrating functional blocks used for implementing marked respirationwaveform generation in accordance with embodiments of the presentinvention. It will be understood by those skilled in the art that thereexist many possible configurations in which these functional blocks canbe arranged and implemented. The examples depicted herein provideexamples of possible functional arrangements used to implement theapproaches of the invention. The components and functionality depictedas separate or discrete blocks/elements in the figures in general can beimplemented in combination with other components and functionality. Thedepiction of such components and functionality in individual or integralform is for purposes of clarity of explanation, and not of limitation.It is also understood that the components and functionality depicted inthe Figures and described herein can be implemented in hardware,software, or a combination of hardware and software.

Various modifications and additions can be made to the preferredembodiments discussed herein without departing from the scope of thepresent invention. Accordingly, the scope of the present inventionshould not be limited by the particular embodiments described above, butshould be defined only by the claims set forth below and equivalentsthereof.

1. A method for characterizing respiration of a patient, comprising:acquiring a respiration waveform; detecting one or more characteristicsassociated with the respiration, wherein detecting the one or morecharacteristics associated with the respiration includes: a) detectingone or more characteristics associated with disordered breathing; and b)determining a type of the disordered breathing; detecting a triggeringevent; and generating a marked respiration waveform in response to thetriggering event using the respiration waveform and one or more symbolsindicating the one or more characteristics associated with therespiration, the one or more symbols including: a) a first symbolindicating a first respiration characteristic selected from the one ormore characteristics associated with the disordered breathing and, b) asecond symbol indicating a second respiration characteristic differentfrom the first respiration characteristic, the first and second symbolsbeing aligned relative to the respiration waveform to indicate times ofoccurrence of the first and second respiration characteristicsrespectively, and wherein the first symbol is selected based on thedetermination of the type of disordered breathing; wherein at least oneof acquiring, detecting, and generating is performed at least in partimplantably.
 2. The method of claim 1, wherein all of acquiring,detecting, and generating are performed at least in part implantably. 3.The method of claim 1, wherein acquiring the respiration waveformcomprises sensing one or more of transthoracic impedance and airflow. 4.The method of claim 1, wherein the triggering event comprises adisordered breathing event.
 5. The method of claim 1, wherein detectingthe one or more characteristics associated with the disordered breathingcomprises detecting a duration of the disordered breathing.
 6. Themethod of claim 1, wherein the type of the disordered breathingcomprises any combination of central and obstructive disorderedbreathing.
 7. The method of claim 1, wherein the type of the disorderedbreathing comprises one or more of sleep disordered breathing andperiodic breathing.
 8. The method of claim 1, wherein determining thetype of the disordered breathing comprises any combination of apnea andhypopnea.
 9. The method of claim 1, wherein the type of the disorderedbreathing comprises Cheyne-Stokes respiration.
 10. The method of claim1, wherein detecting the one or more characteristics associated with therespiration comprises determining any combination of respiration rate,respiration volume, and minute ventilation.
 11. The method of claim 1,wherein detecting the one or more characteristics associated with therespiration comprises determining one or more morphological features ofthe respiration waveform.
 12. The method of claim 11, whereindetermining the one or more morphological features of the respirationwaveform comprises determining one or both of an inspiration durationand an expiration duration.
 13. The method of claim 11, whereindetermining the one or more morphological features of the respirationwaveform comprises determining one or both of an expiration slope and aninspiration slope.
 14. The method of claim 1, further comprisingacquiring one or more additional waveforms, wherein generating themarked respiration waveform comprises generating the marked respirationwaveform using the one or more additional waveforms.
 15. The method ofclaim 14, wherein generating the marked respiration waveform using theone or more additional waveforms comprises time aligning the respirationwaveform and the one or more additional waveforms.
 16. The method ofclaim 14, wherein acquiring the one or more additional waveformscomprises acquiring a cardiac waveform.
 17. The method of claim 1,further comprising transmitting information about at least one of therespiration waveform, the one or more characteristics associated withthe respiration, and the marked respiration waveform.
 18. The method ofclaim 1, further comprising displaying the marked respiration waveform.19. The method of claim 1, further comprising storing information aboutat least one of the respiration waveform, the one or morecharacteristics associated with the respiration, and the markedrespiration waveform.